rs77009095

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003664.5(AP3B1):​c.1969-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 1,593,932 control chromosomes in the GnomAD database, including 4,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 326 hom., cov: 32)
Exomes 𝑓: 0.071 ( 3930 hom. )

Consequence

AP3B1
NM_003664.5 intron

Scores

2
Splicing: ADA: 0.0003659
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.179
Variant links:
Genes affected
AP3B1 (HGNC:566): (adaptor related protein complex 3 subunit beta 1) This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. The encoded protein is part of the heterotetrameric AP-3 protein complex which interacts with the scaffolding protein clathrin. Mutations in this gene are associated with Hermansky-Pudlak syndrome type 2. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
Variant 5-78116244-C-T is Benign according to our data. Variant chr5-78116244-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AP3B1NM_003664.5 linkuse as main transcriptc.1969-10G>A intron_variant ENST00000255194.11 NP_003655.3 O00203-1A0A0S2Z5J4
AP3B1NM_001271769.2 linkuse as main transcriptc.1822-10G>A intron_variant NP_001258698.1 O00203-3A0A0S2Z5J4
AP3B1NM_001410752.1 linkuse as main transcriptc.1969-10G>A intron_variant NP_001397681.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AP3B1ENST00000255194.11 linkuse as main transcriptc.1969-10G>A intron_variant 1 NM_003664.5 ENSP00000255194.7 O00203-1

Frequencies

GnomAD3 genomes
AF:
0.0531
AC:
8077
AN:
152090
Hom.:
327
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0129
Gnomad AMI
AF:
0.0329
Gnomad AMR
AF:
0.0530
Gnomad ASJ
AF:
0.0793
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.0538
Gnomad FIN
AF:
0.0688
Gnomad MID
AF:
0.0538
Gnomad NFE
AF:
0.0777
Gnomad OTH
AF:
0.0660
GnomAD3 exomes
AF:
0.0594
AC:
14856
AN:
250254
Hom.:
543
AF XY:
0.0619
AC XY:
8377
AN XY:
135408
show subpopulations
Gnomad AFR exome
AF:
0.0108
Gnomad AMR exome
AF:
0.0374
Gnomad ASJ exome
AF:
0.0893
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0556
Gnomad FIN exome
AF:
0.0690
Gnomad NFE exome
AF:
0.0785
Gnomad OTH exome
AF:
0.0719
GnomAD4 exome
AF:
0.0709
AC:
102280
AN:
1441724
Hom.:
3930
Cov.:
27
AF XY:
0.0711
AC XY:
51103
AN XY:
718722
show subpopulations
Gnomad4 AFR exome
AF:
0.0118
Gnomad4 AMR exome
AF:
0.0405
Gnomad4 ASJ exome
AF:
0.0893
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.0560
Gnomad4 FIN exome
AF:
0.0701
Gnomad4 NFE exome
AF:
0.0777
Gnomad4 OTH exome
AF:
0.0659
GnomAD4 genome
AF:
0.0530
AC:
8073
AN:
152208
Hom.:
326
Cov.:
32
AF XY:
0.0529
AC XY:
3935
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.0129
Gnomad4 AMR
AF:
0.0529
Gnomad4 ASJ
AF:
0.0793
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.0541
Gnomad4 FIN
AF:
0.0688
Gnomad4 NFE
AF:
0.0777
Gnomad4 OTH
AF:
0.0648
Alfa
AF:
0.0696
Hom.:
79
Bravo
AF:
0.0514
Asia WGS
AF:
0.0230
AC:
79
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineFeb 21, 20131969-10G>A in intron 17 of AP3B1: This variant is not expected to have clinical significance because it has been identified in 7.5% (642/8600) of European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs77009095). -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -
Hermansky-Pudlak syndrome 2 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Hermansky-Pudlak syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
13
DANN
Benign
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00037
dbscSNV1_RF
Benign
0.15
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77009095; hg19: chr5-77412068; API